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| | <StructureSection load='2qs3' size='340' side='right'caption='[[2qs3]], [[Resolution|resolution]] 1.76Å' scene=''> | | <StructureSection load='2qs3' size='340' side='right'caption='[[2qs3]], [[Resolution|resolution]] 1.76Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2qs3]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QS3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QS3 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2qs3]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QS3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QS3 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=UBE:3-({3-[(2S)-2-AMINO-2-CARBOXYETHYL]-5-METHYL-2,6-DIOXO-3,6-DIHYDROPYRIMIDIN-1(2H)-YL}METHYL)-5-PHENYLTHIOPHENE-2-CARBOXYLIC+ACID'>UBE</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.76Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2f34|2f34]], [[2f35|2f35]], [[2f36|2f36]], [[1txf|1txf]], [[2qs1|2qs1]], [[2qs2|2qs2]], [[2qs4|2qs4]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=UBE:3-({3-[(2S)-2-AMINO-2-CARBOXYETHYL]-5-METHYL-2,6-DIOXO-3,6-DIHYDROPYRIMIDIN-1(2H)-YL}METHYL)-5-PHENYLTHIOPHENE-2-CARBOXYLIC+ACID'>UBE</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Grik1, Glur5 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</td></tr>
| + | |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2qs3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qs3 OCA], [https://pdbe.org/2qs3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qs3 RCSB], [https://www.ebi.ac.uk/pdbsum/2qs3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qs3 ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2qs3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qs3 OCA], [https://pdbe.org/2qs3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qs3 RCSB], [https://www.ebi.ac.uk/pdbsum/2qs3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qs3 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/GRIK1_RAT GRIK1_RAT]] Ionotropic glutamate receptor. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. May be involved in the transmission of light information from the retina to the hypothalamus.<ref>PMID:16540562</ref>
| + | [https://www.uniprot.org/uniprot/GRIK1_RAT GRIK1_RAT] Ionotropic glutamate receptor. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. May be involved in the transmission of light information from the retina to the hypothalamus.<ref>PMID:16540562</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Buffalo rat]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Alushin, G M]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Jane, D E]] | + | [[Category: Alushin GM]] |
| - | [[Category: Mayer, M L]] | + | [[Category: Jane DE]] |
| - | [[Category: Cell junction]] | + | [[Category: Mayer ML]] |
| - | [[Category: Glycoprotein]]
| + | |
| - | [[Category: Ion transport]]
| + | |
| - | [[Category: Ionic channel]]
| + | |
| - | [[Category: Membrane protein]]
| + | |
| - | [[Category: Phosphorylation]]
| + | |
| - | [[Category: Postsynaptic cell membrane]]
| + | |
| - | [[Category: Receptor]]
| + | |
| - | [[Category: Rna editing]]
| + | |
| - | [[Category: Synapse]]
| + | |
| - | [[Category: Transmembrane]]
| + | |
| - | [[Category: Transport]]
| + | |
| Structural highlights
Function
GRIK1_RAT Ionotropic glutamate receptor. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. May be involved in the transmission of light information from the retina to the hypothalamus.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Kainate receptors (KARs) are involved in both NMDA receptor-independent long-term potentiation (LTP) and synaptic facilitation at mossy fibre synapses in the CA3 region of the hippocampus. However, the identity of the KAR subtypes involved remains controversial. Here we used a highly potent and selective GluK1 (formerly GluR5) antagonist (ACET) to elucidate roles of GluK1-containing KARs in these synaptic processes. We confirmed that ACET is an extremely potent GluK1 antagonist, with a Kb value of 1.4+/-0.2 nM. In contrast, ACET was ineffective at GluK2 (formerly GluR6) receptors at all concentrations tested (up to 100 microM) and had no effect at GluK3 (formerly GluR7) when tested at 1 microM. The X-ray crystal structure of ACET bound to the ligand binding core of GluK1 was similar to the UBP310-GluK1 complex. In the CA1 region of hippocampal slices, ACET was effective at blocking the depression of both fEPSPs and monosynaptically evoked GABAergic transmission induced by ATPA, a GluK1 selective agonist. In the CA3 region of the hippocampus, ACET blocked the induction of NMDA receptor-independent mossy fibre LTP. To directly investigate the role of pre-synaptic GluK1-containing KARs we combined patch-clamp electrophysiology and 2-photon microscopy to image Ca2+ dynamics in individual giant mossy fibre boutons. ACET consistently reduced short-term facilitation of pre-synaptic calcium transients induced by 5 action potentials evoked at 20-25Hz. Taken together our data provide further evidence for a physiological role of GluK1-containing KARs in synaptic facilitation and LTP induction at mossy fibre-CA3 synapses.
ACET is a highly potent and specific kainate receptor antagonist: characterisation and effects on hippocampal mossy fibre function.,Dargan SL, Clarke VR, Alushin GM, Sherwood JL, Nistico R, Bortolotto ZA, Ogden AM, Bleakman D, Doherty AJ, Lodge D, Mayer ML, Fitzjohn SM, Jane DE, Collingridge GL Neuropharmacology. 2009 Jan;56(1):121-30. Epub 2008 Aug 22. PMID:18789344[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Mayer ML, Ghosal A, Dolman NP, Jane DE. Crystal structures of the kainate receptor GluR5 ligand binding core dimer with novel GluR5-selective antagonists. J Neurosci. 2006 Mar 15;26(11):2852-61. PMID:16540562 doi:26/11/2852
- ↑ Dargan SL, Clarke VR, Alushin GM, Sherwood JL, Nistico R, Bortolotto ZA, Ogden AM, Bleakman D, Doherty AJ, Lodge D, Mayer ML, Fitzjohn SM, Jane DE, Collingridge GL. ACET is a highly potent and specific kainate receptor antagonist: characterisation and effects on hippocampal mossy fibre function. Neuropharmacology. 2009 Jan;56(1):121-30. Epub 2008 Aug 22. PMID:18789344 doi:10.1016/j.neuropharm.2008.08.016
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